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Method for enhancing embryo implantation

A technology of embryos and implantation, which is applied in medical formulas, contraceptives, and medical devices, etc.

Pending Publication Date: 2021-03-16
新生命私人有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although copper has previously been reported to trigger increased endometrial VEGF production in IUCD users (Xin et al., 2004; Rafi et al., 2013), it has not been known so far whether it is a "burst" exposure to copper ions or an IUCD "foreign body" Exceptionally so-called copper delivery elicits a similar VEGF response without causing endometrial disruption such as that seen in IUCD users (Sadovsky et al., 1975; Stanford and Mikolajczyk, 2002)

Method used

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  • Method for enhancing embryo implantation
  • Method for enhancing embryo implantation
  • Method for enhancing embryo implantation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0092] Example 1 Effect of metal ions on the production of LIF and VEGF in vitro

[0093] Materials and methods

[0094] The response of endometrium to copper and zinc metal ions (Cu 2+ and Zn 2+ )Reaction. Cells were grown in Ishikawa medium at 37°C in air with 5% CO 2 Grow in T75 flasks (Nalge NuncInternational, Rochester, NY, United States of America) under the gas environment, described medium is supplemented with 5% fetal calf serum (Invitrogen Corp, Carlsbad, CA, United States of America) αMEM (Sigma-Aldrich), 2 mM Glutamine (Sigma-Aldrich), 1% non-essential amino acids (Sigma-Aldrich), antibiotic free. The medium was refreshed every 48 hours. Cells were subcultured using 0.25% trypsin / EDTA (Invitrogen). For metal ion exposure experiments, cells were seeded on 2-well chamber slides (Ibidi, Martinsried, Germany). After the endometrial cells attached and reached 80-90% confluency, they were exposed to copper and zinc metal ions using two methods (saline solution or ...

Embodiment 2

[0103] The influence of embodiment 2 metal ions on embryonic development and attachment

[0104] Materials and methods

[0105] Ishikawa cells were seeded onto 2-well chamber slides in Ishikawa medium until they reached 80-90% confluency. Then, 5 minutes before exposure to metal implants, the medium was changed to G2 embryo medium and Ishikawa cells were exposed to copper, zinc, or copper-zinc bimetallic implants for a duration of 2 or 5 minutes (or kept unexposed (control)), and the resulting G2 medium was collected after 8 hours. The supernatant was then analyzed as described in Example 1 above to confirm that metal implant exposure resulted in an upregulation of endometrial LIF and VEGF production (see Figures 6A to 6D ).

[0106] To determine whether metal ions can enhance embryo implantation, compacted mouse embryos were exposed to "conditioned media" prior to growth assays. Specifically, nucleated oocytes were collected from superovulated female F1 mice approximatel...

Embodiment 3

[0112] Example 3 Prophetic Example of Treatment to Improve Implantation of Implanted Embryos

[0113] Preparations containing CuCl at a concentration of 150 µM 2 and 100 μM ZnCl 2 isotonic saline solution.

[0114] A 35-year-old woman who experienced repeated implantation failure (RIF), specifically five failed IVF cycles with high-quality embryos, presented 5 days before the expected further transfer of IVF embryos. Use CuCl loaded with a volume of 200 μl usually used for intrauterine insemination therapy 2 / ZnCl 2 Solution graft catheters (such as Soft-Pass TM Catheter for artificial insemination; Cook Medical Inc., Bloomington, IN, USA), the solution was administered into the uterine cavity.

[0115] On the scheduled date for embryo transfer, the woman in question was seen again and received high-quality embryos according to the usual protocol.

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Abstract

A method of enhancing embryo implantation in a subject is disclosed which comprises administering to the uterine cavity of the subject a formulation comprising copper and / or zinc in an amount effective to stimulate endometrial production of leukaemia inhibitory factor (LIF) and / or vascular endothelial growth factor (VEGF). Alternatively, a device may be inserted into the uterine cavity of the subject, wherein the device comprises copper and / or zinc, for a period of time that is effective to stimulate endometrial production of LIF and / or VEGF. The method is suitable for use with women undergoing treatment by any of the assisted reproductive technologies, such as those involving the transfer of embryos such as in vitro fertilisation (IVF) and variants including IVF-ICSI (intracytoplasmic sperm injection) and in vitro maturation (IVM) treatments, as well as intrauterine-insemination (IUI) therapy. However, the method is also applicable for women wanting to improve their prospects of pregnancy through natural conception.

Description

technical field [0001] This disclosure relates to the field of assisted reproductive technologies such as in vitro fertilization (IVF). More specifically, the present disclosure relates to methods as well as formulations and devices for enhancing implantation of implanted embryos in a subject. [0002] priority document [0003] This application claims priority to Australian Provisional Patent Application No. 2018901900, entitled "Method forenhancing embryo implantation", filed 29 May 2018, the contents of which are incorporated by reference in their entirety This article. Background technique [0004] While tremendous advances in IVF treatment over the past three decades have greatly advanced the understanding of how to optimize embryo development in vitro, little progress has been made in methods for optimizing or enhancing successful implantation of transferred embryos. Even today, the transfer of a well-formed, genetically normal embryo into the uterus of a "fertile" ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/34A61K33/26A61P15/08A61P41/00A61B17/435A61F6/14
CPCA61P15/08A61K9/0039A61K9/0034A61K33/34A61K33/30A61K9/08A61K9/51A61K33/06A61K33/242A61K2300/00A61K9/14A61B17/435A61M31/00A61M2205/02A61D19/04A61F6/14A61B17/43A61P43/00A61L29/16A61L2300/102A61K47/02A61K9/06A61K47/10A61K47/38
Inventor K·P·特里梅伦D·K·加德纳A·J·哈维
Owner 新生命私人有限公司
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